The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy. Thus, the combination treatments stimulated the trafficking of pre-existing endogenous effector T cells as well as their intratumoral activation and were more successful than current immunotherapies, which fail due to tumor-intrinsic resistance mechanisms.

中文翻译：

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从头诱导肿瘤内淋巴样结构和血管正常化可增强抗药性肿瘤的免疫治疗。

肿瘤微环境赋予了对抗癌免疫治疗的深刻抵抗力。通过将LIGHT（一种细胞因子TNF超家族）的成员通过血管靶向肽（VTP）靶向肿瘤血管，我们开发了一种具有双重功能的试剂，该试剂具有调节血管生成脉管和诱导三级淋巴结构（TLS）的双重能力。LIGHT-VTP触发了内源性T细胞流入对免疫疗法有抵抗力的本地或同源肿瘤。LIGHT-VTP结合检查点抑制产生了大量的肿瘤内效应子和记忆T细胞，从而带来生存益处，而添加抗肿瘤疫苗则达到了最大的治疗效果。因此，